Recovery of renal function following acute renal failure is dependent on the replacement of necrotic tubular cells with functioning renal epithelium. The source of these new tubular cells is thought to be adjacent, less damaged tubular cells although extrarenal cells contribute to some degree. We hypothesize that a stem cell is present in the adult kidney that can differentiate into the different cell lineages of the kidney. We have isolated and begun to characterize such stem cells derived from adult kidneys that we will refer to as multipotent renal progenitor cells (MRPCs). The source for MRPCs include adult mouse and rat kidneys derived from normal and transgenic animals. The goal of this developmental application is to further characterize these cells, and to use the cells in a culture system model to define factors responsible for cell lineage progression of renal cells. We propose to localize MRPCs in normal and injured adult kidneys and to perform fate mapping of these cells to determine if these cells contribute to tubular cell regeneration following acute tubular necrosis (ATN). We also propose to test whether injected cells at various stages of differentiation can be used as therapeutic agents for the treatment of kidney disease. [unreadable] [unreadable] [unreadable] [unreadable]